The Harvard Medical School Pathways curriculum: A comprehensive curricular evaluation.

PURPOSE: The Harvard Medical School Pathways curriculum represents a major reform effort. Our goals were to enhance reasoning and clinical skills and improve the learning environment and students' approach to learning via use of collaborative, case-based pedagogy; early clinical exposure; and enhanced approaches to teaching and evaluating clinical skills. We evaluated the impact of Pathways on key outcomes related to these goals. MATERIALS AND METHODS: In this prospective, mixed-methods study, we compared the last prior-curriculum cohort (2014 matriculation, n = 135) and first new-curriculum cohort (2015 matriculation, n = 135). Measures included Likert-type surveys, focus groups, and test scores to assess outcomes. RESULTS: Compared with prior-curriculum students, new-curriculum students reported higher mean preclerkship learning environment ratings (Educational Climate Inventory, 62.4 versus 51.9, p < 0.0001) and greater satisfaction with the quality of their preclerkship education (88% versus 73%, p = 0.0007). Mean USMLE Step-1 and Step-2 scores did not differ between groups. At graduation, new-curriculum students rated their medical school experience higher in 6 of 7 domains, including 'fostering a culture of curiosity and inquiry' (4.3 versus 3.9, p = 0.006) and focus on 'student-centered learning' (3.9 versus 3.4, p = 0.002). CONCLUSIONS: The new curriculum outperformed or was equal to the prior one on most measures of learning environment and perceived quality of education, without a decline in medical knowledge or clinical skills. Robust longitudinal evaluation provided important feedback for ongoing curriculum improvement.

Advanced Integrated Science Courses: Building a Skill Set to Engage With the Interface of Research and Medicine.

Scientific research has been changing medical practice at an increasing pace. To keep up with this change, physicians of the future will need to be lifelong learners with the skills to engage with emerging science and translate it into clinical care. How medical schools can best prepare students for ongoing scientific change remains unclear. Adding to the challenge is reduced time allocated to basic science in curricula and rapid expansion of relevant scientific fields. A return to science with greater depth after clinical clerkships has been suggested, although few schools have adopted such curricula and implementation can present challenges. The authors describe an innovation at Harvard Medical School, the Advanced Integrated Science Courses (AISCs), which are taken after core clerkships. Students are required to take 2 such courses, which are offered in a variety of topics. Rather than factual content, the learning objectives are a set of generalizable skills to enable students to critically evaluate emerging research and its relationship to medical practice. Making these generalizable skills the defining principle of the courses has several important advantages: it allows standardization of acquired skills to be combined with diverse course topics ranging from basic to translational and population sciences; students can choose courses and projects aligned with their interests, thereby enhancing engagement, curiosity, and career relevance; schools can tailor course offerings to the interests of local faculty; and the generalizable skills delineate a unique purpose of these courses within the overall medical school curriculum. For the 3 years AISCs have been offered, students rated the courses highly and reported learning the intended skill set effectively. The AISC concept addresses the challenge of preparing students for this era of rapidly expanding science and should be readily adaptable to other medical schools.

Machine-learning-based predictions of direct-acting antiviral therapy duration for patients with hepatitis C.

INTRODUCTION: Hepatitis C, which affects 71 million persons worldwide, is the most common blood-borne pathogen in the United States. Chronic infections can be treated effectively thanks to the availability of modern direct-acting antiviral (DAA) therapies. Real-world data on the duration of DAA therapy, which can be used to optimize and guide the course of therapy, may also be useful in determining quality of life enhancements based upon total required supply of medication and long-term improvements to quality of life. We developed a machine learning model to identify patient characteristics associated with prolonged DAA treatment duration. METHODS: A nationwide U.S. commercial managed care plan with claims data that covers about 60 million beneficiaries from 2009 to 2019 were used in the retrospective study. We examined differences in age, gender, and multiple comorbidities among patients treated with different durations of DAA treatment. We also examined the performance of machine learning models for predicting a prolonged course of DAA based on the area under the receiver operating characteristic curve (AUC). RESULTS: We identified 3943 cases with hepatitis C who received sofosbuvir/ledipasvir as the first course of DAA and were eligible for the study. Patients receiving prolonged treatment (n = 240, 6.1%) were more likely to have compensated cirrhosis, decompensated cirrhosis, and other comorbidities (P < 0.001). For distinguishing patients who received prolonged DAA treatment for hepatitis C from patients received standard treatment, the optimal predictive model, constructed with XGBoost, had an AUC of 0.745 ± 0.031 (P < 0.001). CONCLUSIONS: The risk of antiviral resistance and the cost of DAA are strong motivators to ensure that first-round DAA therapy is effective. For the dominant DAA treatment during the course of this analysis, we present a model that identifies factors already captured in established guidelines and adds to those age, comorbidity burden, and type 2 diabetes status; patient characteristics that are predictive of extended treatment.

The 2020 Nobel Prize for Medicine or Physiology for the Discovery of Hepatitis C Virus: A Triumph of Curiosity and Persistence.

The 2020 Nobel Prize in Medicine or Physiology was awarded to Drs. Harvey Alter, Michael Houghton, and Charles Rice for their contributions to the discovery and characterization of the hepatitis C virus (HCV). Their achievements represent a remarkable triumph of biomedical science which allowed the development of curative therapy for HCV, that will save countless lives. This tribute provides a historical perspective of the laureates' seminal work leading to the discovery of the HCV and a synopsis of a forum hosted by the American Association for the Study of Liver Diseases to honor the laureates in which they offered their perspectives, advice for young investigators and what's left to accomplish in the field. Finally, others in the research community who have worked closely with one or more of the laureates, share some of their personal reflections and anecdotes.

Hepatic gap junctions amplify alcohol liver injury by propagating cGAS-mediated IRF3 activation.

Alcohol-related liver disease (ALD) accounts for the majority of cirrhosis and liver-related deaths worldwide. Activation of IFN-regulatory factor (IRF3) initiates alcohol-induced hepatocyte apoptosis, which fuels a robust secondary inflammatory response that drives ALD. The dominant molecular mechanism by which alcohol activates IRF3 and the pathways that amplify inflammatory signals in ALD remains unknown. Here we show that cytoplasmic sensor cyclic guanosine monophosphate-adenosine monophosphate (AMP) synthase (cGAS) drives IRF3 activation in both alcohol-injured hepatocytes and the neighboring parenchyma via a gap junction intercellular communication pathway. Hepatic RNA-seq analysis of patients with a wide spectrum of ALD revealed that expression of the cGAS-IRF3 pathway correlated positively with disease severity. Alcohol-fed mice demonstrated increased hepatic expression of the cGAS-IRF3 pathway. Mice genetically deficient in cGAS and IRF3 were protected against ALD. Ablation of cGAS in hepatocytes only phenocopied this hepatoprotection, highlighting the critical role of hepatocytes in fueling the cGAS-IRF3 response to alcohol. We identified connexin 32 (Cx32), the predominant hepatic gap junction, as a critical regulator of spreading cGAS-driven IRF3 activation through the liver parenchyma. Disruption of Cx32 in ALD impaired IRF3-stimulated gene expression, resulting in decreased hepatic injury despite an increase in hepatic steatosis. Taken together, these results identify cGAS and Cx32 as key factors in ALD pathogenesis and as potential therapeutic targets for hepatoprotection.

The Harvard Medical School Pathways Curriculum: Reimagining Developmentally Appropriate Medical Education for Contemporary Learners.

As the U.S. health care system changes and technology alters how doctors work and learn, medical schools and their faculty are compelled to modify their curricula and teaching methods. In this article, educational leaders and key faculty describe how the Pathways curriculum was conceived, designed, and implemented at Harvard Medical School. Faculty were committed to the principle that educators should focus on how students learn and their ability to apply what they learn in the evaluation and care of patients. Using the best evidence from the cognitive sciences about adult learning, they made major changes in the pedagogical approach employed in the classroom and clinic. The curriculum was built upon 4 foundational principles: to enhance critical thinking and provide developmentally appropriate content; to ensure both horizontal integration between courses and vertical integration between phases of the curriculum; to engage learners, foster curiosity, and reinforce the importance of student ownership and responsibility for their learning; and to support students' transformation to a professional dedicated to the care of their patients and to their obligations for lifelong, self-directed learning.The practice of medicine is rapidly evolving and will undoubtedly change in multiple ways over the career of a physician. By emphasizing personal responsibility, professionalism, and thinking skills over content transfer, the authors believe this curriculum will prepare students not only for the first day of practice but also for an uncertain future in the biological sciences, health and disease, and the nation's health care system, which they will encounter in the decades to come.

Do Professionalism Lapses in Medical School Predict Problems in Residency and Clinical Practice?

PURPOSE: Recognizing that physicians must exhibit high levels of professionalism, researchers have attempted to identify the precursors of clinicians' professionalism difficulties, typically using retrospective designs that trace sanctioned physicians back to medical school. To better establish relative risk for professionalism lapses in practice, however, this relationship must also be studied prospectively. Therefore, this study investigated the sequelae of medical school professionalism lapses by following students with medical school professionalism problems into residency and practice. METHOD: Beginning in 2014, 108 graduates from Harvard Medical School and Case Western Reserve University School of Medicine who appeared before their schools' review boards between 1993 and 2007 for professionalism-related reasons were identified, as well as 216 controls matched by sex, minority status, and graduation year. Prematriculation information and medical school performance data were collected for both groups. Outcomes for the groups were studied at 2 points in time: ratings by residency directors, and state medical board sanctions and malpractice suits during clinical practice. RESULTS: Compared with controls, students who appeared before their schools' review boards were over 5 times more likely to undergo disciplinary review during residency (16% vs 3%, respectively) and almost 4 times more likely to require remediation or counseling (35% vs 9%, respectively). During clinical practice, 10% of those who had made review board appearances were sued or sanctioned vs 5% of controls. Logistic regression for these outcomes indicated, however, that professional lapses in medical school were not the only, or even the most important, predictor of problems in practice. CONCLUSIONS: Students with professionalism lapses in medical school are significantly more likely to experience professionalism-related problems during residency and practice, although other factors may also play an important predictive role.

A snapshot of underrepresented physicians 15 years after medical school.

We conducted a study to compare medical school experiences, values, career paths, and career satisfaction of under-represented in medicine (URiM) and non-URiM physicians approximately 15 years after medical school, guided by the Theory of Planned Behavior and the concept of stereotype threat. The sample consisted of four graduating classes, 1996-1999, of Harvard Medical School, 20% of whom were URiM. URiM respondents came from families of lower educational attainment and graduated with more debt. As students, they reported a greater experience of stereotype threat and, and at graduation they showed a tendency to place a higher value on avoiding a career that places them under constant pressure. Concerning their current status, URiM respondents expressed a lower level of satisfaction with their career progress. Multivariable analyses indicated that across the entire sample, URiM status was not a significant predictor of employment in academic medicine, but that being in academic medicine was predicted by mentors' encouragement for a research career, greater intention to pursue research, and a lower value on having a financially rewarding career. Lower career satisfaction was predicted by one's status as URiM, employment in academic medicine, greater involvement in research, and a greater value on avoiding constant pressure. The data suggest that negative student experiences in medical school, combined with the lack of mentor encouragement and financial pressures may discourage URiM medical students from pursuing academic careers, and that pressures for productivity and working in academic medicine may degrade the satisfaction derived by physicians in general.

Computed Tomography Findings as a Novel Predictor of Alcohol-Associated Hepatitis Outcomes.

BACKGROUND: Accurate prediction of outcomes for alcohol-associated hepatitis (AH) is critical, as prognosis determines treatment eligibility. Computed tomography (CT) features may provide prognostic information beyond traditional models. AIMS: Our aim was to identify CT features that predict outcomes in AH. METHODS: We studied 108 patients retrospectively with definite or probable AH, who underwent admission abdominal CT. A radiologist blinded to outcome evaluated eight CT features. The primary outcome was 90-day mortality. RESULTS: Twenty-five (23.2%) patients died within 90 days. While traditional prognostic tools, including Maddrey discriminant function (DF), predicted 90-day mortality (OR 1.01 [1.00, 1.03], P = 0.02), abdominal CT findings were also accurate predictors. On abdominal CT, patients with severe AH had larger volume of ascites (moderate/large volume: 34.0 vs. 8.2%, P < 0.0001), longer liver length (17.1 vs. 15.1 cm, P = 0.001), greater liver heterogeneity (moderate/severe: 21.3 vs. 8.2%, P = 0.007), and more likely to have splenomegaly (42.6 vs. 18.0%, P = 0.009) than those with mild AH. Univariate analysis revealed that ascites volume (OR 2.59 [1.35, 4.96], P = 0.004) predicted 90-day mortality. In multivariate analysis, degree of ascites predicted 90-day mortality when controlling for Maddrey DF (OR 2.36 [1.19, 4.69], P = 0.01) and trended toward significance when controlling for MELD score (OR 2.02 [0.95, 4.30], P = 0.07). CONCLUSION: CT findings in AH differentiate disease severity and predict 90-day mortality; therefore, the role of CT warrants further investigation as a tool in AH management.

Physicians' Perspectives on Palliative Care for Patients With End-Stage Liver Disease: A National Survey Study.

Specialty palliative care (PC) is underused for patients with end-stage liver disease (ESLD). We sought to examine attitudes of hepatologists and gastroenterologists about PC for patients with ESLD. We conducted a cross-sectional survey of these specialists who provide care to patients with ESLD. Participants were recruited from the American Association for the Study of Liver Diseases membership directory. Using a questionnaire adapted from prior studies, we examined physicians' attitudes about PC and whether these attitudes varied based on patients' candidacy for liver transplantation. We identified predictors of physicians' attitudes about PC using linear regression. Approximately one-third of eligible physicians (396/1236, 32%) completed the survey. Most (95%) believed that centers providing care to patients with ESLD should have PC services, and 86% trusted PC clinicians to care for their patients. Only a minority reported collaborating frequently with inpatient (32%) or outpatient (11%) PC services. Most believed that when patients hear the term PC, they feel scared (94%) and anxious (87%). Most (83%) believed that patients would think nothing more could be done for their underlying disease if a PC referral was suggested. Physicians who believed that ESLD is a terminal condition (B = 1.09; P = 0.006) reported more positive attitudes about PC. Conversely, physicians with negative perceptions of PC for transplant candidates (B = -0.22; standard error = 0.05; P < 0.001) reported more negative attitudes toward PC. In conclusion, although most hepatologists and gastroenterologists believe that patients with ESLD should have access to PC, they reported rarely collaborating with PC teams and had substantial concerns about patients' perceptions of PC. Interventions are needed to overcome misperceptions of PC and to promote collaboration with PC clinicians for patients with ESLD.

Barriers to Use of Palliative Care and Advance Care Planning Discussions for Patients With End-Stage Liver Disease.

BACKGROUND & AIMS: Despite evidence for the benefits of palliative care (PC) referrals and early advance care planning (ACP) discussions for patients with chronic diseases, patients with end-stage liver disease (ESLD) often do not receive such care. We sought to examine physicians' perceptions of the barriers to PC and timely ACP discussions for patients with ESLD. METHODS: We conducted a cross-sectional survey of hepatologists and gastroenterologists who provide care to adult patients with ESLD, recruited from the American Association for the Study of Liver Diseases 2018 membership registry. Using a questionnaire adapted from prior studies, we assessed physicians' perceptions of barriers to PC use and timely ACP discussions; 396 of 1236 eligible physicians (32%) completed the questionnaire. RESULTS: The most commonly cited barriers to PC use were cultural factors that affect perception of PC (by 95% of respondents), unrealistic expectations from patients about their prognosis (by 93% of respondents), and competing demands for clinicians' time (by 91% of respondents). Most respondents (81%) thought that ACP discussions with patients who have ESLD typically occur too late in the course of illness. The most commonly cited barriers to timely ACP discussions were insufficient communication between clinicians and families about goals of care (by 84% of respondents) and insufficient cultural competency training about end-of-life care (81%). CONCLUSION: There are substantial barriers to use of PC and timely discussions about ACP-most hepatologists and gastroenterologists believe that ACP occurs too late for patients with ESLD. Strategies are needed to overcome barriers and increase delivery of high-quality palliative and end-of-life care to patients with ESLD.

Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT.

BACKGROUND AND OBJECTIVES: Literature on the prognosis of patients with cirrhosis who require RRT for AKI is sparse and is confounded by liver transplant eligibility. An update on outcomes in the nonlisted subgroup is needed. Our objective was to compare outcomes in this group between those diagnosed with hepatorenal syndrome and acute tubular necrosis, stratifying by liver transplant listing status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective cohort study of patients with cirrhosis acutely initiated on hemodialysis or continuous RRT at five hospitals, including one liver transplant center. Multivariable regression and survival analysis were performed. RESULTS: Four hundred seventy-two subjects were analyzed (341 not listed and 131 listed for liver transplant). Among nonlisted subjects, 15% (51 of 341) were alive at 6 months after initiating RRT. Median survival was 21 (interquartile range [IQR], 8, 70) days for those diagnosed with hepatorenal syndrome and 12 (IQR, 3, 43) days for those diagnosed with acute tubular necrosis (P=0.25). Among listed subjects, 48% (63 of 131) received a liver transplant. Median transplant-free survival was 15 (IQR, 5, 37) days for those diagnosed with hepatorenal syndrome and 14 (IQR, 4, 31) days for those diagnosed with acute tubular necrosis (P=0.60). When stratified by transplant listing, with adjusted Cox models we did not detect a difference in the risk of death between hepatorenal syndrome and acute tubular necrosis (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.59 to 1.11, among those not listed; HR, 0.73; 95% CI, 0.44 to 1.19, among those listed). CONCLUSIONS: Cause of AKI was not significantly associated with mortality in patients with cirrhosis who required RRT. Among those not listed for liver transplant, mortality rates were extremely high in patients both with hepatorenal syndrome and acute tubular necrosis. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_09_CJASNPodcast_18_1_A.mp3.

Academic Performance on First-Year Medical School Exams: How Well Does It Predict Later Performance on Knowledge-Based and Clinical Assessments?

Number of appearances in the bottom quartile of 1st-year medical school exams were used to represent the extent to which students were having academic difficulties. Medical educators have long expressed a desire to have indicators of medical student performance that have strong predictive validity. Predictors traditionally used fell into 4 general categories: demographic (e.g., gender), other background factors (e.g., college major), performance/aptitude (e.g., medical college admission test scores), and noncognitive factors (e.g., curiosity). These factors, however, have an inconsistent record of predicting student performance. In comparison to traditional predictive factors, we sought to determine the extent to which academic performance in the 1st-year of medical school, as measured by examination performance in the bottom quartile of the class in 7 required courses, predicted later performance on a variety of assessments, both knowledge based (e.g., United States Medical Licensing Examination Step 1 and Step IICK) and clinical skills based (e.g., clerkship grades and objective structured clinical exam performance). Of all predictors measured, number of appearances in the bottom quartile in Year 1 was the most strongly related to performance in knowledge-based assessments, as well as clinically related outcomes, and, for each outcome, bottom-quartile performance accounted for additional variance beyond that of the traditional predictors. Low academic performance in the 1st year of medical school is a meaningful risk factor with both predictive validity and predictive utility for low performance later in medical school. The question remains as to how we can incorporate this indicator into a system of formative assessment that effectively addresses the challenges of medical students once they have been identified.

Medical Students Who Pursue a Joint MD/MBA Degree: Who Are They and Where Are They Heading?

Increasingly, health care is being delivered in large, complex organizations, and physicians must learn to function effectively in them. As a result, several medical and business schools have developed joint programs to train physician leaders who receive both medical degree (MD) and master of business administration (MBA) degrees. We examined several themes in relation to these programs, revolving around concerns about who is attracted to them and whether exposure to the differing cultures of medicine and business have an impact on the professional identities of their graduates as manifested in their motivations, aspirations, and careers. We addressed these issues by studying students in the joint MD/MBA program at Harvard Medical School (HMS) and Harvard Business School (HBS). Our data came from several internal sources and a survey of all students enrolled in the joint program in spring 2013. We found relatively few differences between joint program students and equivalent cohorts of HMS students in terms of personal characteristics, preadmission performance, and performance at HMS and HBS. Contrary to the concerns that such programs may draw students away from medicine, the vast majority embraced careers involving extensive postgraduate medical training, with long-term plans that leveraged their new perspectives and skills to improve health care delivery.

Factors associated with physicians' choice of a career in research: a retrospective report 15 years after medical school graduation.

Relatively little is known regarding factors associated with the choice of a research career among practicing physicians, and most investigations of this issue have been conducted in the absence of a theoretical/conceptual model. Therefore we designed a survey to identify the determinants of decisions to pursue a biomedical research career based upon the Theory of Planned Behavior and the concept of stereotype threat. From October 2012 through January 2014 electronic surveys were sent to four consecutive Harvard Medical School graduating classes, 1996-1999. Respondents provided demographic information, indicated their current research involvement, and provided retrospective reports of their experiences and attitudes when they were making career choices as they completed medical school. Multivariable ordinal regression was used to identify factors independently associated with current research involvement. Completed questionnaires were received from 358 respondents (response rate 65 %). In unadjusted analyses, variables associated with more extensive research involvement included non-minority status, male gender, lower debt at graduation, strong attitudes toward research at time of graduation, and greater social pressures to pursue research (all P < .001). These associations remained significant in multivariable regression analysis (all P < 0.01). However, an interaction between sex and prior research publications was also detected, indicating that more extensive research involvement during medical school doubled the likelihood of a research career for women (OR 2.53, 95 % CI 1.00-6.40; P = 0.05). Most of the factors predicting research career choice involve factors that are potentially modifiable, suggesting that appropriately designed behavioral interventions may help to expand the size and diversity of the biomedical research community.